Safety, Tolerability and Pharmacokinetics of Single Rising and Multiple Oral Doses of Telmisartan / Hydrochlorothiazide (HCTZ) in Healthy Male Volunteers

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses (40 mg Telmisartan / 12.5 mg HCTZ to 80 mg Telmisartan / 12.5 mg HCTZ) and Multiple Oral Doses (80 mg Telmisartan / 12.5 mg HCTZ) of Drug in Healthy Male Volunteers

Group 1:

To investigate safety, tolerability and pharmacokinetics of Telmisartan + HCTZ (T40/H12.5 and T80/H12.5)

Group 2:

To investigate safety, tolerability and pharmacokinetics of Telmisartan + HCTZ (T80/H12.5 x 7 days)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Low dose of telmisartan; Drug: High dose of telmisartan; Drug: HCTZ

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males according to the following criteria: No finding deviating of clinical relevance and no evidence of a clinically relevant concomitant disease based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead ECG, clinical laboratory tests
• Age ≥20 and Age ≤35 years
• Body Mass Index (BMI) ≥17.6 and BMI ≤26.4 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with "Good Clinical Practice (GCP)"

Exclusion Criteria:

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Chronic or relevant acute infections
• Any laboratory value outside the reference range that is of clinical relevance
• Positive result for hepatitis B surface (HBs) antigen, anti hepatitis C virus (HCV) antibodies, Syphilitic test or HIV test
• Surgery of gastrointestinal tract (except appendectomy)
• History of relevant orthostatic hypotension (mean standing SBP varies by ≥ 20 mmHg from mean supine systolic blood pressure (SBP) and/or mean standing diastolic blood pressure (DBP) varies by ≥ 10 mmHg from mean supine DBP), fainting spells or blackouts.
• History of hepatic dysfunction (e.g. biliary cirrhosis, cholestasis)
• History of serious renal dysfunction
• History of bilateral renal artery stenosis or renal artery stenosis in a solitary kidney
• History of cerebrovascular disorder
• History of hyperkalemia
• Known hypersensitivity to any component of the formulation; known hypersensitivity to any other angiotensin II receptor antagonist; known hypersensitivity to sulfonamides or sulphonamide-derived drugs (e.g. thiazides)
• History of impaired glucose tolerance
• History of hypokalemia
• History of hyperuricemia
• Salt restriction therapy
• Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 7 days prior to administration or during the trial
• Participation in another trial with an investigational drug within four months or 6 half-lives of the investigational drug, whichever is longer, prior to administration or during the trial
• Smoker (more than 20 cigarettes /day)
• Alcohol abuse
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within seven days prior to administration)
• Intake of alcohol within two days prior to administration
• Inability to comply with dietary regimen of study centre
• Inability to comply with smoking cessation during hospitalization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single low dose Telmisartan with HCTZ	Drug: Low dose of telmisartan; Drug: HCTZ
Experimental: Single high dose Telmisartan with HCTZ	Drug: High dose of telmisartan; Drug: HCTZ
Experimental: Multiple high dose Telmisartan with HCTZ	Drug: High dose of telmisartan; Drug: HCTZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events		up to 10 days after last drug administration
Number of patients with clinically relevant findings in physical examination		up to 10 days after last drug administration
Number of patients with clinically relevant findings in vital signs	blood pressure, pulse rate, body temperature	up to 10 days after last drug administration
Number of patients with clinically relevant findings in 12-lead ECG		up to 10 days after last drug administration
Number of patients with clinically relevant findings in clinical laboratory tests		up to 10 days after last drug administration
Global assessment of tolerability by the investigator	verbal rating scale	up to 10 days after last drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration of the analytes in plasma (Cmax)	Up to 96 hours after drug administration
Area under the concentration time curve of the analytes in plasma (AUC)	Up to 96 hours after drug administration
Time from dosing to maximum concentration of the analytes in plasma (tmax)	Up to 96 hours after drug administration
Terminal rate constant of the analytes in plasma (λz)	Up to 96 hours after drug administration
Terminal half-life of the analytes in plasma (t1/2)	Up to 96 hours after drug administration
Mean residence time of the analytes in the body after po administration (MRTpo)	Up to 96 hours after drug administration
Apparent clearance of the analytes in the plasma after extravascular administration (CL/F)	Up to 96 hours after drug administration
Apparent volume of distribution of the analytes in plasma during the terminal phase λz following an extravascular dose (Vz/F)	Up to 96 hours after drug administration
Amount of HCTZ that is eliminated in urine from the time interval t1 to t2 (Aet1-t2)	Up to 48 hours after drug administration
Fraction of HCTZ excreted unchanged in urine from time point t1 to t2 (fet1-t2)	Up to 48 hours after drug administration
Renal clearance of HCTZ in plasma from the time point t1 until the time point t2 (CLR, t1-t2)	Up to 48 hours after drug administration
Minimum measured concentration of the analytes in plasma at steady state over a uniform dosing interval τ (Cmin,ss)	Up to 96 hours after drug administration
Average concentration of the analytes in plasma at steady state (Cavg)	Up to 96 hours after drug administration
Accumulation ratio of the analytes in plasma after multiple dose administration over a uniform dosing interval τ (RA)	Up to 96 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2003
• Primary Completion (Actual): February 15, 2004

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimated): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: 502.453